Diuretics such as the thiazides and pyrazines are useful as antihypertensive agents. However, these diuretics tend to increase circulating plasma renin levels. This increase in renin may be undesirable since it acts to reduce the antihypertensive effect of the diuretic.
.beta.-adrenergic blocking agents are another class of drugs which are effective in long term treatment of hypertension. Propranalol, a .beta.-adrenergic blocking agent, has been found to inhibit renal renin secretion in man and in animals [New England Journal of Medicine 287, 1209-1213 (1972)] Pindolol, another .beta.-adrenergic blocking agent, has been found to have antihypertensive effect when administered alone and in combination with a thiazide diuretic [The Medical Journal of Australia 2, 309-312, (1972)]. The effect on hypertension of a combination of large doses of 4 different .beta.-blocking agents (including a substituted 1,2,5-thiadiazole) with a thiazide diuretic, has also been reported (Postgraduate Medical Journal 50, 253-259, May, 1974).
It has been discovered that administration of a particular combination of a substituted 1,2,5 thiadiazole .beta.-adrenergic blocking agent and said diuretic to a hypertensive animal (1) enhances the antihypertensive activity of the diuretic and (2) reduces the severity of potassium loss due to the diuretic.